1. Field of the Invention
The present invention relates to an apparatus and a method for measuring a weight load exerted by a leg of a lab animal. Specifically, the invention relates to an apparatus and a method for estimating the degree of pain felt by an animal on the basis of a weight load exerted by a limb suffering diverse inflammation.
2. Description of the Related Art
The most representative symptom reported by patients suffering diseases such as arthritis is pain in the affected area. This pain can aggravate the condition through a neurogenic inflammation. Namely, an arthritic pain due to inflammation in a peripheral tissue stimulates a primary afferent nerve fiber through various mediators that carries the inflammation, and thus excitability of the primary afferent nerve fiber is increased. The increase in excitability reaches spinal neurons, and as a result, hyperalgesia is induced. Therefore, a full knowledge of the pain will play an important role in understanding and overcoming the disease.
There are various behavioral testing methods, using lab animals, for inspecting the degree of pain due to a disease such as arthritis.
A method of measuring the degree of pain is disclosed in articles entitled 1) xe2x80x9cReduction in locomotor activity of arthritic rats as parameter for chronic pain: effect of morphine, acetylsalicylic acid and citalopramxe2x80x9d by Lassen J J and Arnt J, Acta. Pharmacol. Toxicol. (Copenh)., 1985, 57(5), pp. 345., 2) xe2x80x9cPain-related disability and effects of chronic morphine in the adjuvant-induced arthritis model of chronic painxe2x80x9d by Cain C K, Francis J M, Plone M A, Emerich D F and Lindner M D, Physiol. Behav., 1997, 62(1), pp. 199, 3) xe2x80x9cEstablishment of behavioral parameters for the evaluation of osteopathic treatment principles in a rat model of arthritisxe2x80x9d by Hallas B, Lehman S, Bosak A, Tierney S, Galler R, Jacovina P, Scandalis T A and Wells M, J. Am. Osteopath. Assoc., 1997, 97(4), pp. 207, and so on. In this method, a decrease of whole activities of a lab animal having arthritis in a leg is expressed numerically by recording changes in the activities of the lab animal through video analysis. The decrease of whole activity of the lab animal is due to an arthritic pain. This method is considered as a highly reliable test because it can quantify the decrease of the whole activities of lab animals. However, it is difficult to define whether whole activities directly relates to the pain. Also, the method is very expensive and takes much time.
Another method of measuring the arthritic pain felt by a lab animal is disclosed in articles entitled 1) xe2x80x9cDifferent effects of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on spinal release of amino acids after development of acute arthritis in ratsxe2x80x9d by Sluka K A, Jordan H H, Willis W D and Westlund K N, Brain. Res., 1994, 664(1-2), pp. 77, 2) xe2x80x9cNicotinic cholinergic receptors: potential targets for inflammatory pain reliefxe2x80x9d by Lawand N B, Lu Y and Westlund, K N, Pain, 1999, 80(1-2), pp. 291, and 3) xe2x80x9cGabapentin attenuates nociceptive behaviors in an acute arthritis model in ratsxe2x80x9d by Lu Y and Westlund K N, J. Pharmacol. Exp. Ther., 1999, 290(1), pp. 214. In this method, arthritis is induced in the right leg of a lab animal such as rat by injecting kaolin and carrageenan (suspended in normal saline) into the knee joint cavity; and then the sole of the right foot is stimulated with heat. Thereafter, latency of leg withdrawal response to the heat is measured as a degree of the pain. However, the response of the leg against the heat is considered as a secondary hyperalgesia that inflammation of the knee affects the leg by sensitization of central neuron. Therefore, it is difficult to ascertain whether the method measures the pain caused by the inflammation induced in the knee.
Further, alternative methods of evaluating inflammation caused in a leg by threshold for vocalization or local temperature are known. The threshold value is measured when an inflamed leg of a lab animal is stimulated with pressure and thus the lab animal shrieks with pain, and the local temperature is measured at an inflamed portion. However, the threshold value and the local temperature are not objective and quantitative factors for representing change in primary behavior aspect induced by the pain.
In order to conduct a more accurate behavioral test, a method of evaluating an arthritic pain using decrease of weight load applied in an inflamed leg of a lab animal is disclosed in articles entitled 1) xe2x80x9cArthritis induced in cat by sodium urate: A possible lab animal for tonic painxe2x80x9d by Okuda K, Nakahama H, Miyakawa H and Shima K, Pain, 1984, 18, pp. 287, 2) xe2x80x9cDifferential fore- and hindleg force transmission in the walking ratxe2x80x9d by Clarke K A, Physiol. Behav., 1995, 58(3), pp. 415, 3) xe2x80x9cGait analysis in a rat model of osteoarthrosisxe2x80x9d by Clarke K A, Heitmeyer A G, Smith A G and Taiwo Y O, Physiol. Behav., 1997, 62(5), pp. 951, and 4) xe2x80x9cWeight bearing as an objective measure of arthritic pain in the ratxe2x80x9d by Scxc3x6tt E, Berge O G, xc3x84ngeby-Mxc3x6ller K, Hammarstr m G, Dalsgaard C J and Brodin E, J. Pharmacol. Toxicol. Methods, 1994, 1994 31(2), pp. 79. Such a method is based on the fact that the weight load applied in the inflamed leg is decreased due to the arthritic pain. The decrease of the weight load is considered as an objective and quantitative index for representing change of primary behavior aspect induced by the pain. However, typically, the weight load of the inflamed leg of the lab animal is measured under the condition that the lab animal is made to stand up or remain a stationary state. In this case, the lab animal is stressed because it can not move. As a result, the decrease of the weight load is changed depending on a pose or a stress of the lab animal. In addition, the decrease of the weight load appears more precisely when the lab animal is moving freely. Therefore, it is necessary to minimize artificial restraining or manipulations of experimental animals during measuring of the weight load.
It is, therefore, an objective of the present invention to provide an apparatus and a method with which the weight load of an inflamed limb of a lab animal can be measured objectively and precisely while the lab animal is walking freely in a non-binding state.
In accordance with one aspect of the present invention, there is provided an apparatus for measuring a weight load on a leg of a lab animal, comprising: a long box in which the lab animal moves freely along the length of said long box; and one or more weight sensors attached to the bottom of said long box for measuring the weight load on at least one leg of said lab animal.
In accordance with another aspect of the present invention, there is provided a method of measuring a weight load on a leg of a lab animal, comprising the steps of: providing a box which includes one or more weight sensors to its bottom; causing the lab animal to move through said box; and processing electric signals from said one or more weight sensors to provide information relating to the weight load exerted by a leg of the lab animal.
In accordance with yet another aspect of the present invention, there is provided a method of evaluating severity of pain in an inflamed leg of a lab animal, comprising the steps of: (a) measuring a first weight load on said inflamed leg and a second weight load by an opposite leg to said inflamed leg; and (b) evaluating severity of pain on the basis of said first and said second weight loads, wherein, said measuring step (a) includes the steps of: (a1) providing a box which includes one or more weight sensors to a bottom thereof; (a2) causing the lab animal to walk through said box; and (a3) processing electric signals from said one or more weight sensors to provide information relating to the weight load on said inflamed leg and said opposite leg of the lab animal.
In accordance with yet another aspect of the present invention, there is provided a method of analyzing effects of an analgesic drug on an inflamed leg of an animal, comprising the steps of: (a) providing an animal with inflammation induced in its limb; (b) measuring a first weight load on said limb and a second weight load by another limb opposite to said limb; (c) injecting an analgesic drug into said limb; (d) measuring, after said injecting step (c), a third weight load on said limb and a fourth weight load on said another limb; and (e) computing the ratios of said first weight load to said second weight load and said third weight load to said fourth weight load respectively, to analyze the effects of said analgesic drug, wherein, each of said measuring steps (b) and (d) includes the steps of (bd1) providing a box which includes one or more weight sensors to its bottom; (bd2) causing the lab animal to voluntarily walk through the said box; and (bd3) processing electric signals from said one or more weight sensors to provide information relating to said first to fourth weight loads.